Genetic signatures of high-altitude adaptation in Tibetans

Yang, Jian, Jin, Zi-Bing, Chen, Jie, Huang, Xiu-Feng, Li, Xiao-Man, Liang, Yuan-Bo, Mao, Jian-Yang, Chen, Xin, Zheng, Zhili, Bakshi, Andrew, Zheng, Dong-Dong, Zheng, Mei-Qin, Wray, Naomi R., Visscher, Peter M., Lu, Fan and Qu, Jia (2017) Genetic signatures of high-altitude adaptation in Tibetans. Proceedings of the National Academy of Sciences, 114 16: 4189-4194. doi:10.1073/pnas.1617042114

Author Yang, Jian
Jin, Zi-Bing
Chen, Jie
Huang, Xiu-Feng
Li, Xiao-Man
Liang, Yuan-Bo
Mao, Jian-Yang
Chen, Xin
Zheng, Zhili
Bakshi, Andrew
Zheng, Dong-Dong
Zheng, Mei-Qin
Wray, Naomi R.
Visscher, Peter M.
Lu, Fan
Qu, Jia
Title Genetic signatures of high-altitude adaptation in Tibetans
Journal name Proceedings of the National Academy of Sciences   Check publisher's open access policy
ISSN 1091-6490
Publication date 2017-04-18
Year available 2017
Sub-type Article (original research)
DOI 10.1073/pnas.1617042114
Open Access Status Not yet assessed
Volume 114
Issue 16
Start page 4189
End page 4194
Total pages 6
Place of publication Washington, DC, United States
Publisher National Academy of Sciences
Language eng
Formatted abstract
Indigenous Tibetan people have lived on the Tibetan Plateau for millennia. There is a long-standing question about the genetic basis of high-altitude adaptation in Tibetans. We conduct a genome-wide study of 7.3 million genotyped and imputed SNPs of 3,008 Tibetans and 7,287 non-Tibetan individuals of Eastern Asian ancestry. Using this large dataset, we detect signals of high-altitude adaptation at nine genomic loci, of which seven are unique. The alleles under natural selection at two of these loci [methylenetetrahydrofolate reductase (MTHFR) and EPAS1] are strongly associated with blood-related phenotypes, such as hemoglobin, homocysteine, and folate in Tibetans. The folate-increasing allele of rs1801133 at the MTHFR locus has an increased frequency in Tibetans more than expected under a drift model, which is probably a consequence of adaptation to high UV radiation. These findings provide important insights into understanding the genomic consequences of high-altitude adaptation in Tibetans.
Keyword Genome-wide association study
High-altitude adaptation
Mixed linear model
Polygenic selection
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 2013CB967502
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
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Queensland Brain Institute Publications
Institute for Molecular Bioscience - Publications
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